A compound heterozygote patient with Ehlers-Danlos syndrome type VI has a deletion in one allele and a splicing defect in the other allele of the lysyl hydroxylase gene.

We report the first deletion mutation and the first splicing defect in the lysyl hydroxylase gene in a compound heterozygote patient with Ehlers-Danlos syndrome type VI with markedly reduced lysyl hydroxylase activity. Northern analysis of the RNA isolated from skin fibroblasts of the patient demonstrated the presence of a truncated lysyl hydroxylase mRNA. PCR and sequence analysis confirmed the truncation and indicated that the cells contain two types of shortened mRNAs, one lacking the sequences corresponding to exon 16 and the other lacking that corresponding to exon 17 of the lysyl hydroxylase gene. Analysis of genomic DNA revealed deletion of the penultimate adenosine from the 3' end of intron 15 from one allele. This defect was probably responsible for the skipping of exon 16 sequences from the transcript. The other allele, inherited from the mother, contains an Alu-Alu recombination with a deletion of about 3,000 nucleotides from the gene; this abnormality explains the lack of exon 17 sequences. The identified mutations in exon 16 and exon 17 do not alter the reading frame of the transcripts.